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A Phase II Trial of Neoadjuvant Arimidex With or Without Faslodex in Postmenopausal Women With Hormone Receptor Positive Breast Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

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Trial Information

A Phase II Trial of Neoadjuvant Arimidex With or Without Faslodex in Postmenopausal Women With Hormone Receptor Positive Breast Cancer


Purpose and Objectives

The primary objective of this study is to determine if ER-targeted therapy, ARIMIDEX and
FASLODEX, used in combination is superior to ARMIDEX alone in hormone receptor positive
breast cancer.

Primary study objective 1. To determine the efficacy of primary breast cancer, as measured
by decrease in proliferation (KI67), to the combination of ARIMIDEX, and FASLODEX at high
dose

Secondary study objectives 1. To study molecular changes in response to treatment. 2. To
correlate changes in Ki67 with clinical response 3. To determine the pathologic response
rate. 4. To assess the tolerability and safety of the combination regimen.

This is a phase II randomized multi-center study. As indicated in the study design schema
found in the protocol document attached to Section S, patients will be initially randomized
to receive ARIMIDEX, or ARIMIDEX+FASLODEX (high dose) for 16 weeks (112 days). A
computer-generated randomization scheme will be generated by the study statistician at the
Breast Center, Baylor College of Medicine. A 1:1 randomization scheme using permuted blocks
will be employed. Randomization will be centralized at the Breast Center, Baylor College of
Medicine and accomplished via access to a secure web-based procedure that is currently being
implemented in our other multi-center clinical trials. Enrollment, eligibility, and
randomization information will be stored in an Oracle database on the Breast Center's Sun
server and will be accessible only through secure web-based applications. Communication with
the pharmacy will be handled by email which will contain only patient identification number
and initials and by FAX or hardcopy. The hardcopy will be used by physicians to send to the
pharmacy a signed computer-generated pharmacy order to legally dispense study drug.

Within 30 days prior to randomization subjects will sign the study consent form, and have a
history and physical exam, including all concurrent medications. Blood will be drawn for
CBC, platelets, serum chemistries, BUN, creatinine, and liver function tests. If necessary
to determine menopausal status FSH, LH and serum estradiol will be obtained. An EKG, CXR PA
and lateral will be performed and a bilateral mammogram and US of primary breast cancer will
be done within 90 days of randomization. Subjects will then be randomized to receive either
ARIMIDEX 1 mg po q day (Group A), or ARIMIDEX 1 mg po q day and FASLODEX 500 mg IM, day 1,
day 14, day 28 and thereafter once every 28 days (Group B). Study medications will be
dispensed within 60 days of randomization. On day 28, subjects will be evaluated for side
effects and a second breast core biopsy will be obtained. Evaluation for tumor response and
tolerability of the regimen will be evaluated every 28 days in outpatient clinic visits. ALL
treatment will continue until day 112 when patients with a clinical response or stable
disease will receive appropriate surgical resection. If the tumor is unresectable on day
112, a core needle biopsy will be done. The surgical specimen will be obtained for further
molecular analysis. After surgery, patients will be off study and will receive additional
breast cancer therapy at the discretion of their treating physician. Patients who develop
progressive disease on protocol will be taken off study and offered alternative treatment.
All patients will have a safety follow-up 1 month after the surgery (or the alternative core
biopsy).

Treatment will be administered on outpatient basis. After the baseline breast biopsy,
patients will be randomized to receive ARIMIDEX 1mg po q day (group A), or ARIMIDEX 1mg po q
day with FASLODEX 500 mg day 1, day 14, day 28, and thereafter every 28 days (Group B).
After 28 days a second biopsy will be obtained in all patients. All patients will continue
on the same randomized treatment for the total duration of the study of 112 days till the
day before surgery. No investigational or commercial agents or therapies other than those
described below may be administered with the intent to treat the patient's malignancy.

Study Visit Procedures: Pre-Study Procedures will include the following: informed consent,
breast biopsy, demographics, medical history, concurrent medication list, physical exam,
blood draw, bidimensional tumor measurement, bilateral mammogram, primary breast ultrasound
and chest x-ray.

Day 1 procedures will include the following: study drug administration, clinic visit.

Day 14 procedures will include the following (group B only) study drug injection and clinic
visit.

Day 28 procedures will include the following (group B only) study drug injection. Both group
A and B, breast biopsy, concurrent medication list, physical exam, blood draw, clinic visit,
adverse events evaluation, bidimensional tumor measurement.

Day 56 procedures will include the following (group B only) study drug injection. Both group
A and B, concurrent medication list, physical exam, blood draw, adverse events evaluation,
clinic visit and bidimensional tumor measurement.

Day 84 procedures include (group B only) study drug injection. Both group A and B,
concurrent medication list, physical exam, blood draw, adverse event evaluation, clinic
visit and bidimensional tumor measurement.

Day 112 procedures include study drug administration, concurrent medication list, physical
exam, blood draw, adverse events evaluation, bidimensional tumor measurement, bilateral
mammogram, primary breast ultrasound and tumor resection.

Day 140 procedures include blood draw, clinic visit and safety evaluation for adverse
events.

Duration of Therapy In the absence of treatment delays due to adverse events, treatment will
continue for 4 months or until one of the following criteria applies: Disease progression,
Intercurrent illness that prevents further administration of treatment, Unacceptable adverse
events(s), Patient decides to withdraw from the study, or General or specific changes in the
patient's condition render the patient unacceptable for further treatment in the judgment of
the investigator.

This protocol will close 6 months after the last patient is enrolled. Patients will receive
study medications from day 0 until day 111, which is the day before their planned surgery.
On day 140, patients will have a safety follow up visit and to determine the need for
further treatment after surgery.

Breast Core Biopsy All subjects will have a breast tumor core biopsy at the beginning of the
study, and a second biopsy after 2 weeks. Core needle biopsies are planned because they will
provide sufficient histologically evaluable tissue for the assays proposed in this study.


Inclusion Criteria:



- All subjects must be female.

- Postmenopausal status, defined as any one of the following criteria:

- Documented history of bilateral oophorectomy.

- Age 60 years or more.

- Age 45 to 59 and satisfying one or more of the following criteria:

- Amenorrhea for at least 12 months and intact uterus.

- Amenorrhea for less than 12 months and a follicle stimulating hormone (FSH)
and estradiol concentration within postmenopausal range including: patients
who have had a hysterectomy and patients who have received hormone
replacement.

- Patients must have histologically confirmed invasive breast cancer with a primary
tumor of 3 cm or more in greatest dimension as measured by clinical examination.

- Estrogen receptor and/or progesterone receptor positive disease.

- Patients must not have received any prior treatment for current or newly diagnosed
breast cancer.

- Patients must have not received previous treatment with any of the study medications
or similar drugs.

- No use of selective estrogen receptor modulators (SERM) such as raloxifene or similar
agents in the past 2 years.

- WHO performance status of 0, 1, or 2.

- Adequate organ function defined as follows:

- Adequate renal function, defined by a serum creatinine within 3 times the upper
limits of normal.

- Adequate liver function, defined by total bilirubin, AST, ALT, and alkaline
phosphatase within 3 times the upper limits of normal.

- Adequate bone marrow function, defined as a WBC greater than 3.0 ml, PLT greater
than 75,000/ul, Hb greater than 9 gm/l.

- Willing to undergo breast core biopsies as required by the study protocol. -
Ability to understand and sign a written informed consent for participation in the
trial.

- Life expectancy of at least 1 year.

Exclusion Criteria:

- Premenopausal status.

- Other coexisting malignancies with the exception of basal cell carcinoma or cervical
cancer in situ.

- Patients with brain metastasis.

- WHO performance status of 3 or 4.

- Is judged by the investigator, uncontrolled intercurrent illness including, but not
limited to, ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, significant cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.

- Evidence of any other significant clinical disorder or laboratory finding that makes
it undesirable for the subject to participate in the clinical trial. - Concurrent
treatment with estrogens or progestins. Patients must stop these drugs at least two
weeks prior to study entry.

- Treatment with a non-approved or investigational drug within 30 days before Day 1 of
study treatment.

- Platelet count less than 75,000.

- In the opinion of the investigator, bleeding diathesis or anticoagulation therapy
that would preclude intramuscular injections.

- History of hypersensitivity to castor oil.

- Any evidence of clinically active interstitial lung disease (patients with chronic
stable radiographic changes who are asymptomatic need not be excluded) - Patients
with recurrent breast cancer.

- Patients with contralateral second primary breast cancers are eligible.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary objective of this study is to determine if ER-targeted therapy, ARIMIDEX and FASLODEX, used in combination is superior to ARMIDEX alone in hormone receptor positive breast cancer.

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Mothaffar Rimawi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine

Authority:

United States: Food and Drug Administration

Study ID:

H 20431

NCT ID:

NCT00570323

Start Date:

December 2007

Completion Date:

December 2016

Related Keywords:

  • Breast Cancer
  • Breast Cancer
  • HORMONE RECEPTOR POSITIVE BREAST CANCER
  • Breast Neoplasms

Name

Location

Baylor College of MedicineHouston, Texas  77030
Doctors Hospital of Laredo TexasLaredo, Texas  78041